Technical Field of the Invention
The invention relates to a method for the preparation of a radiopharmaceutical compound, in particular an amino acid derivative useful as a positron emission tomography (PET) tracer. Embodiments of the present invention are especially suitable when automated and offers advantages over known methods. Particularly, the invention relates to a method for preparation of [18F]-1-amino-3-fluorocyclobutane-1-carboxylic acid ([18F]-FACBC, also known as [18F]-fluciclovine).
Description of Related Art
The non-natural amino acid [18F]-1-amino-3-fluorocyclobutane-1-carboxylic acid ([18F]-FACBC, also known as [18F]-Fluciclovine) is taken up specifically by amino acid transporters and has shown promise for tumour imaging with positron emission tomography (PET).
A known synthesis of [18F]-FACBC (EP2017258) begins with the provision of the protected precursor compound 1-(N-(t-butoxycarbonyl)amino)-3-[((trifluoromethyl)sulfonyl)oxy]-cyclobutane-1-carboxylic acid ethyl ester. This precursor compound is first labelled with [18F]-fluoride:
before removal of the two protecting groups:
To then obtain injectable [18F]FACBC drug product the crude [18F]FACBC is purified and then formulated.
In the current routine process for producing [18F]FACBC the radiolabelling step (i) is carried out in a reaction vessel followed by transfer of the radiolabelled compound of Formula II above to a tC 18 solid phase extraction column for removal of the ester protecting group by alkaline hydrolysis. During this time, the reaction vessel is washed several times with water. The ester-deprotected compound is then returned to the reaction vessel for the removal of the Boc protecting group by acid hydrolysis. Despite washing the reaction vessel several times, the present inventors have determined residual acetonitrile levels in formulated [18F]FACBC drug /product ranging from around 100 μg/ml to around 600 μg/ml. While these levels are acceptable in terms of permitted daily exposure and in the context of the acceptance criteria for [18F]FACBC drug product, the amount and observed variability is less than ideal.
There is therefore scope for the provision of an [18F]FACBC drug product wherein the levels of acetonitrile are more tightly controlled, and more particularly within a lower concentration range.